Optimization of Antibiotics in Mothers and their Breastfed Infants Using Pharmacomicrobiomic and Metabolomic Analyses

利用药物微生物组学和代谢组学分析优化母亲及其母乳喂养婴儿的抗生素

• 批准号: 10309708
• 负责人: Lars Bode
• 金额: $ 125万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-10 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10309708
• 关键词: Address; Ampicillin; Analytical Chemistry; Antibiotic Prophylaxis; Antibiotic Therapy; Antibiotics; Basic Science; Biological Assay; Breast Feeding; Breastfed infant; Centers of Research Excellence; Child; Childhood; Clinical; Clinical Pharmacology; Clinical Sciences; Collection; Cytochrome P450; Data; Data Science; Data Scientist; Development; Drug Kinetics; Enrollment; Ensure; Enzymes; Exposure to; Face; Faculty; Fostering; Growth and Development function; Hepatic; High Pressure Liquid Chromatography; Human; Human Milk; Immune; Immune response; Infant; Infection; Infrastructure; Laboratories; Lead; Leadership; Mass Spectrum Analysis; Metabolic; Milk; Mission; Molecular; Mothers; National Institute of Child Health and Human Development; Near-Infrared Spectroscopy; Neonatal; Nutritional; Oligosaccharides; Outcome; Performance; Pharmaceutical Preparations; Pharmacology; Physiological; Pilot Projects; Pneumococcal vaccine; Productivity; Protocols documentation; Public Health; Research; Research Infrastructure; Research Methodology; Research Personnel; Research Project Grants; Resources; Role; Sampling; Serum; Skin; Source; Stress; Technical Expertise; Technology; Therapeutic; Therapeutic Human Experimentation; Training; Validation; cohort; drug metabolism; enzyme activity; experience; fundamental research; immune function; infant monitoring; infant outcome; innovation; metabolome; metabolomics; microbiome; milk microbiome; mouse model; non-invasive monitor; novel; operation; pathogen; pediatric pharmacology; pharmacometrics; physiologic model; programs; response; training opportunity

PROJECT SUMMARY The UC San Diego MPRINT CET, entitled “Optimization of Antibiotics in Mothers and Their Breastfed Infants Using Pharmacomicrobiomic and Metabolomic Analyses”, brings together a team of highly experienced and proven collaborative investigators with leadership roles in maternal and pediatric clinical pharmacology, fundamental research methods and technologies. Across its highly integrated and synergistic components, the UCSD MPRINT CET addresses critical barriers in maternal-infant pharmacology regarding (1) the pharmacokinetics of infant exposure to maternal antibiotic treatment via breastmilk or close contact, (2) the impact of maternal antibiotic therapy or prophylaxis on establishment of the normal infant microbiome and gut metabolome, (3) potential downstream effects of such antibiotic exposure on infant immune function and hepatic cytochrome P450 drug metabolizing enzymes, and (4) the pivotal role of breast milk both as a conduit for antibiotic transfer and source of beneficial human/mammalian milk oligosaccharides (HMOs/MMOs) that may support microbiome and immune integrity in face of antibiotic stress. The successful operation and outcome of our MPRINT CET is accomplished through 3 Projects (Clinical, Basic Science and Data Science) an Administrative Core and two Technology Cores, the Milk Analytics Core (MAC) and Pharmacometrics and Analytical Chemistry Core (PACC). In the Clinical Project “Antibiotic Treatment in Breastfeeding Mothers: Effects on Milk, Microbiome, and Infant Outcomes”, we have proven expertise and infrastructure and access to a high enrolling maternal-infant clinical cohort to study how maternal antibiotics alter breast milk composition and impact infant outcomes in clinical meaningful ways. In the Basic Science Project “The Impact of Ampicillin and Breast Milk Oligosaccharides on the Infant Microbiome and Immune Functions”, we leverage extensive experience in mouse models of neonatal host-pathogen interactions to probe functional effects of ampicillin and MMOs on infant immune function, including a novel cross-fostering strategy with wild-type and MMO-deficient mothers. In our Data Science Project “Impact of Maternal Antibiotics on the Breastfeeding Infant Microbiome and Metabolome”, we deploy advanced MS technology, non-invasive sampling and innovative molecular networking analytics in a cutting-edge study of the impact of breast milk antibiotic exposure on the infant microbiome, metabolome and hepatic Cyp enzymes. The MAC provides milk collection protocols and kits, near infrared spectroscopy and HPLC, HMO/MMO and nutritional composition analysis, and new assay validation expanding our MPRINT CET analytical capabilities, while the PAC develops and validates novel quantitative assays and physiologic and semi-physiologic models to describe and predict maternal and infant antibiotic PK during breastfeeding. Our Administrative Core oversees integration and performance of our research projects/cores and their milestones, connecting them to the national MPRINT CET HUB and unique training/pilot projects.

项目总结